PrOD was approved in December 2014. In October 2015, the Food and Drug Administration (FDA) updated guidance based on 26 cases worldwide “of worsening liver injury, hepatic decompensation, and liver failure,” Dr. Butt said. The guidance was focused on patients with pretreatment advanced liver disease, especially those with moderate-to-severe hepatic impairment, or Child-Pugh B/C. In most cases, the liver injury occurred within 1–4 weeks of starting treatment.

Another protease inhibitor-containing regimen “might also be associated with hepatic decompensation during or following drug exposure,” he said. “Anecdotal reports also suggest a possible association with advanced chronic kidney disease.” However, “large-scale studies are not available to quantify the risk.”

To quantify the incidence and risk of hepatic decompensation in patients treated with PrOD as well as those who developed worsening of renal function on or after treatment with PrOD, Dr. Butt and colleagues analyzed data from ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) to identify patients treated with a PrOD regimen who had hepatic decompensation, Fib-4 cirrhosis, a MELD score of >3.5, diabetes, and progressive chronic kidney disease. ERCHIVES includes all patients who are positive or negative for the hepatitis C virus (HCV), based on an HCV antibody test between 2001 and 2015.

Excluded were patients with HIV co-infection, those who were HBsAg+, had hepatic decompensation or hepatocellular carcinoma prior to baseline, a missing baseline Fib-4 score, or no post-treatment initiation follow-up.

A total of 3,728 patients on PrOD were identified, with 22.8% presenting with baseline cirrhosis. The study patients were followed for up to 12 weeks following treatment completion.

Overall, 15 cases of hepatic decompensation events occurred, for an incidence rate of 10.6 (95% CI: 5.89–17.36) per 1,000 patient-years. The rate was 36.91 (95% CI: 19.07–64.46) among patients with baseline cirrhosis vs. a rate of 2.73 (95% CI: 0.56–7.97) among those without.

Incidence rate for patients with a MELD score >9 was 27.48 (95% CI: 10.09–59.82) per 1,000 person-years compared with 7.72 (95% CI: 3.53–14.65) for those with a MELD score ≤9.